Compliance with oral medications is often poor, which costs the US healthcare industry billions of dollars and contributes to ~100,000 premature deaths each year. The likelihood for compliance is greatly increased for medications that are administered as once-weekly medications compared to once-daily regimens. This transformation can be accomplished by increasing the residence time of drug delivery devices within the GI tract. Previous strategies aimed at increasing the residence time of devices (e.g. buoyant gastric devices, expandable gastroretention devices, and mucoadhesive materials) have achieved only partial success, to date. This project will leverage in-house expertise in biodegradable elastomers, polymer processing, and pigment- based underwater adhesives to produce a device-based oral delivery system that can increase the residence time within the small intestine of the GI tract by 10X from 20 h to > 200h. The key innovation in this approach is the use of textured device-based mucoadhesives. Specifically, a conformal expandable device will mechanically interlock with the villi of the small intestine. Mechanical interlocking increases mucoadhesion at the tissue-device interface, which will resist peristalsis and therefore increase the characteristic residence time for devices transiting the GI track. Devices will be composed of dual-crosslinked biodegradable elastomeric networks that are packaged into a temporary form factor for facile transit through the stomach using a pH- sensitive polymer encapsulant. Upon reaching the small intestine, the pH-sensitive polymer will dissolve and the drug-loaded device will expand to anchor the device within the lumen. This project will quantify in vitro device performance by measuring figures of merit such as friction forces and the work of adhesion as a function of physical parameters and device geometry. The timeline for gastric transit will be quantified using X- ray imaging to measure the in vivo gastric transit of devices loaded with X-ray contrast agent in minipigs. The oral bioavailability of a model peptide will also be measured. This project has the potential to advance a transformative device-based mucoadhesive that can increase patient compliance for orally administered medications. Furthermore, a controlled release device that stably resides in the GI tract could enable the delivery of bioactive therapeutics with poor bioavailability or extremely short half-lives such as low molecular weight peptides. Taken together, this technology could improve the administration of many orally administered therapeutics to manage disease states such as inflammatory bowel disease, obesity, or Type 2 diabetes.